Anti-angiogenic therapy has fundamentally landmarked the clinical new era of anti-cancer therapy. It was demonstrated that the blockade of vascular endothelial growth factor results in regression of the disease and prolongation of survival. In contrast, it was clarified that the differential sensitivity of the therapeutic impact exists. Many thought-provoking questions have been raised in this field. Herein, we focus on the clinical data and attempt to summarize some clinical trials of anti-angiogenic treatment, highlighting the sparkling articles, the differential sensitivities to these agents beyond progression continuation, and how to individualize treatment according to validated biomarkers.